Antigenic variation of Anaplasma marginale msp2 occurs by combinatorial gene conversion

Molecular Microbiology
Kelly A BraytonAnthony F Barbet

Abstract

The rickettsial pathogen Anaplasma marginale establishes lifelong persistent infection in the mammalian reservoir host, during which time immune escape variants continually arise in part because of variation in the expressed copy of the immunodominant outer membrane protein MSP2. A key question is how the small 1.2 Mb A. marginale genome generates sufficient variants to allow long-term persistence in an immunocompetent reservoir host. The recombination of whole pseudogenes into the single msp2 expression site has been previously identified as one method of generating variants, but is inadequate to generate the number of variants required for persistent infection. In the present study, we demonstrate that recombination of a whole pseudogene is followed by a second level of variation in which small segments of pseudogenes recombine into the expression site by gene conversion. Evidence for four short sequential changes in the hypervariable region of msp2 coupled with the identification of nine pseudogenes from a single strain of A. marginale provides for a combinatorial number of possible expressed MSP2 variants sufficient for lifelong persistence.

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Citations

Apr 6, 2005·FEMS Microbiology Reviews·Gustavo Santoyo, David Romero
Jan 30, 2004·Molecular and Biochemical Parasitology·David R Allred, Basima Al-Khedery
Mar 24, 2004·Veterinary Microbiology·Jose C Garcia-GarciaKatherine M Kocan
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Jun 9, 2009·Nature Reviews. Microbiology·Kirk W DeitschJames R Stringer
Feb 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·James E FutseGuy H Palmer
Oct 4, 2011·Molecular Biology and Evolution·Daniel RejmanekJanet Foley
Jul 24, 2012·Nucleic Acids Research·Yoshikazu Furuta, Ichizo Kobayashi
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Sep 23, 2003·Infection and Immunity·Quan LinNing Zhi
Jun 24, 2004·Infection and Immunity·Quan LinZerai Woldehiwet
Jul 21, 2005·Journal of Bacteriology·Laura BaldoJohn H Werren

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